In Vivo Applications of Photoswitchable Bioactive Compounds

Gomila, Alexandre M. J.; Gorostiza, Pau

doi:10.1002/9783527827626.ch34

Cited by 2 publications

(2 citation statements)

References 129 publications

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“…Its binding pocket is highly conserved throughout species. 13,59 The simplicity of the network in zebrafish and its close resemblance to higher mammals, along with the advantages of using an established neuropharmacological [61][62][63][64] and photopharmacological 5,65 animal model, allowed us to investigate the effects of photorexin on locomotor activities of wildtype larvae.…”

Section: B)mentioning

confidence: 99%

In vivo photocontrol of orexin receptors with a nanomolar light-regulated analogue of orexin-B

Prischich,

Sortino,

Gomila-Juaneda

et al. 2023

Preprint

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Orexinergic neurons are critically involved in regulating arousal, wakefulness, and appetite. Their dysfunction has been associated with sleeping disorders, and non-peptide drugs are currently being developed to treat insomnia and narcolepsy. Yet, no light-regulated agents are available to reversibly control their activity. To meet this need, a photoswitchable peptide analogue of the endogenous neuroexcitatory peptide orexin-B was designed, synthesized, and tested in vitro and in vivo. This compound (photorexin) is the first photo-reversible ligand reported for orexin receptors. It allows dynamic control of activity in vitro (including full agonism, nanomolar activity, and subtype selectivity to human OX2 receptors) and in vivo in zebrafish larvae by direct application in water. Photorexin induces dose- and light-dependent changes in locomotion and a reduction in the successive induction reflex that is associated with sleep behavior. Molecular dynamics calculations indicate that trans and cis photorexins adopt similar bent conformations and that the only discriminant between their structures and activities is the positioning of the N-terminus at the extracellular region of the orexin receptor. Thus, our approach could be extended to a broad and important family of neuropeptides that share a “message-address” mechanism when binding to their cognate receptors.

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Section: B)mentioning

confidence: 99%

In vivo photocontrol of orexin receptors with a nanomolar light-regulated analogue of orexin-B

Prischich,

Sortino,

Gomila-Juaneda

et al. 2023

Preprint

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“…An alternative strategy involves conferring photosensitivity upon bioactive small molecules. [2] This is frequently achieved by introducing or substituting specific components of their structure with molecular photoswitches [3] -substances that exhibit reversible alterations in properties (such as shape and polarity) upon exposure to light, with azobenzene derivatives [4] being the most commonly used. This emerging approach known as "photopharmacology" [5] has given rise to a plethora of compounds with potential antimicrobial [6] and anticancer applications.…”

Section: Introductionmentioning

confidence: 99%

Reversible Influence of Hemipiperazine Photochromism on the Early Development of Zebrafish Embryo

Seliwjorstow,

Takamiya,

Rastegar

et al. 2024

ChemBioChem

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This study explores the potential of controlling organismal development with light by using reversible photomodulation of activity in bioactive compounds. Specifically, our research focuses on plinabulin 1, an inhibitor of tubulin dynamics that contains a photochromic motif called hemipiperazine. The two isomeric forms, Z‐1 and E‐1, can partially interconvert with light, yet show remarkable thermal stability in darkness. The Z‐isomer exhibits higher cytotoxicity due to stronger binding to α‐tubulin's colchicine site. The less toxic E‐1 form, considered a "pro‐drug", can be isolated in vitro and stored. Upon activation by blue or cyan light, it predominantly generates the more toxic Z‐1 form. Here we demonstrate that 1 can effectively photomodulate epiboly, a critical microtubule‐dependent cell movement during gastrulation in zebrafish embryos. This research highlights the potential of photomodulation for precise and reversible control of cellular activities and organismal development.

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In Vivo Applications of Photoswitchable Bioactive Compounds

Cited by 2 publications

References 129 publications

In vivo photocontrol of orexin receptors with a nanomolar light-regulated analogue of orexin-B

In vivo photocontrol of orexin receptors with a nanomolar light-regulated analogue of orexin-B

Reversible Influence of Hemipiperazine Photochromism on the Early Development of Zebrafish Embryo

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